Mixed

There's a lot to cover in the category of mixed insulins, as they can be animal origin, r-DNA/GE/GM origin or analog insulins. The non-analog mixed insulins are made up of intermediate-actingNPH/isophane insulin and short-actingR/neutral. normal insulin. The analog mixes are made from intermediate-acting protamine-suspended analog insulin (suspended similar to NPH/isophane insulin) and fast-acting analog insulin. They can also vary in the fraction (amount or percent) of the two types (R/neutral and NPH/isophane) of insulin used to make a non-analog mix, and in the percentage of fast/rapid-acting analog insulin and slower-acting protamine suspended analog insulin.

For some reason, those in the US choose to list the slower, NPH/isophane based insulin fraction first, such as Humulin or Novolin 70/30. The rest of the world gives the faster insulin top billing and the result is 30/70 [1]. Regardless of how this is written, it means that the insulin is made up of 70% NPH/isophane insulin and 30% R/neutral insulin.

The most common mixes are 70/30 (30/70) (non analog) or 75/25 (25/75) (analog). There are no currently-marketed mixes which combine insulins of different origins. Eli Lilly's form of beef/pork Iletin and Novo Nordisk's Lentard were discontinued some time ago.

For the most part, non-mixed Intermediate-acting insulins are generally used for dogs with diabetes. Here are the most common ones that could cause confusion:

Contents

British National Formulary [2] classes all of them as biphasic [3] insulins--having more than one activity or action. Regardless of their origin, the two actions are that of the fast/rapid or short acting insulin in combination with the intermediate-acting isophane or isophane-suspended analog insulin. The activity profiles of the mixed or biphasic insulins vary by whether they are analog or non-analog insulins and the fractions of the faster and slower insulins used in the mix.

There are other various mixes (all human origin) on the market in other countries; the R/neutral fraction or percentage ranges from 10 to 50. In the US, only 70/30 remains on the market, with a wider range available in other parts of the world.

Direct comparison of insulin activity profiles for Lente and 70/30 insulins. The early strong action from the non-suspended R/neutral/normal insulin is seen at the "bump" from hours 0-6.

Let's look at the differences in the two insulins. Lente is comprised of 70 % long-actingUltralente insulin and 30% short-actingSemilente insulin. So proportions of a long-acting and short-acting insulin are being combined to produce a intermediate-acting insulin. Both Ultralente and Semilente insulin are suspended by adding zinc and the size of their respective insulin crystals. The largest insulin crystals are those of Ultralente, while Semilente contains the smallest, or microcrystals. Simply put, you're combining a long insulin and a short insulin to make an intermediate-acting one.

70/30 insulin starts with 70% NPH/isophane insulin, an intermediate-acting insulin which is suspended by protamine. To that, 30% R/neutral/normal insulin, which is short-acting and soluble, meaning there is no suspension; nothing is added to this insulin to delay its action. In this case, you are taking an intermediate-acting insulin with a suspension and adding to it a short-acting one with no suspension to create an intermediate-acting insulin.

So we have an insulin (Lente), made up of a long-acting and short-acting insulin, both with zinc suspensions, and a mixed insulin (70/30), made from an intermediate-acting protamine suspended insulin and a short-acting one without any suspension. Because of these differences, the insulin action profile for these two insulins is going to be quite different, even though both insulins are classed as intermediate-acting.

These are not as widely varied. The "basics" are that they most commonly come in 70/30 (30/70) or 75/25 (25/75) fractions. Made of either insulin aspart (Novo) or insulin lispro (Lilly), they are a combination of the fast/rapid acting analog insulin and the same analog insulin which has been "slowed down" by a process of creating special crystals of either insulin aspart or insulin lispro with protamine suspension.

The same is true for analog mixed insulins as for non-analog ones regarding the US listing the percentage or fraction of the slower insulin first and everyone else choosing to list the faster action portion that way.